Passive immunotherapy with potent antibodies could find application in a number of aspects of HIV-1 infection, including the prevention of infection after accidental exposure to the virus, the interruption of transmission of virus from mother to child, and the reduction of viral load in combination with anti-retroviral drugs. Three human monoclonal antibodies (b12, 2G12 and 2F5) and an immunoadhesin (CD4-IgG2) show promise as potential immunotherapeutics by their ability to neutralize a wide range of primary isolates of HIV-1. Our aim is to evaluate the anti-viral efficacy of these antibodies, singly and in combination, in vivo in the hu-PBL-SCID mouse model. The specific aims of this proposal are: (1) To determine the in vitro neutralization properties of a number of antibodies, individually and in combination, for a chosen set of primary isolates (2) To determine the ability of antibodies alone and in combination to protect hu-PBL-SCID mice against challenge with primary isolates. (3) To determine the properties of in vitro selected neutralization escape mutants of primary viruses in the mouse model and the ability of antibodies of protect against these viruses (4) To attempt to generate escape mutants in vivo. The emerging results should assist in the design of immunotherapeutic strategies using neutralizing antibodies and illuminate areas of potential concern such as neutralization escape.